EP1427465B1 - Powder inhaler - Google Patents
Powder inhaler Download PDFInfo
- Publication number
- EP1427465B1 EP1427465B1 EP02764384.0A EP02764384A EP1427465B1 EP 1427465 B1 EP1427465 B1 EP 1427465B1 EP 02764384 A EP02764384 A EP 02764384A EP 1427465 B1 EP1427465 B1 EP 1427465B1
- Authority
- EP
- European Patent Office
- Prior art keywords
- inhaler
- compartment
- compartments
- cartridge
- sealing layer
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 239000000843 powder Substances 0.000 title claims description 12
- 239000011888 foil Substances 0.000 claims description 70
- 239000003814 drug Substances 0.000 claims description 21
- 238000007789 sealing Methods 0.000 claims description 21
- 238000006073 displacement reaction Methods 0.000 claims description 7
- 239000002184 metal Substances 0.000 claims 1
- 230000010355 oscillation Effects 0.000 claims 1
- 230000000007 visual effect Effects 0.000 claims 1
- 230000000694 effects Effects 0.000 description 5
- 229940079593 drug Drugs 0.000 description 3
- KWGRBVOPPLSCSI-WPRPVWTQSA-N (-)-ephedrine Chemical compound CN[C@@H](C)[C@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WPRPVWTQSA-N 0.000 description 2
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 2
- GIIZNNXWQWCKIB-UHFFFAOYSA-N Serevent Chemical compound C1=C(O)C(CO)=CC(C(O)CNCCCCCCOCCCCC=2C=CC=CC=2)=C1 GIIZNNXWQWCKIB-UHFFFAOYSA-N 0.000 description 2
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 2
- UCTWMZQNUQWSLP-UHFFFAOYSA-N adrenaline Chemical compound CNCC(O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-UHFFFAOYSA-N 0.000 description 2
- -1 anti-inflammatory Chemical compound 0.000 description 2
- OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 description 2
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 238000002483 medication Methods 0.000 description 2
- LMOINURANNBYCM-UHFFFAOYSA-N metaproterenol Chemical compound CC(C)NCC(O)C1=CC(O)=CC(O)=C1 LMOINURANNBYCM-UHFFFAOYSA-N 0.000 description 2
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 229960002657 orciprenaline Drugs 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 2
- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 1
- AKNNEGZIBPJZJG-MSOLQXFVSA-N (-)-noscapine Chemical compound CN1CCC2=CC=3OCOC=3C(OC)=C2[C@@H]1[C@@H]1C2=CC=C(OC)C(OC)=C2C(=O)O1 AKNNEGZIBPJZJG-MSOLQXFVSA-N 0.000 description 1
- UBLVUWUKNHKCJJ-ZSCHJXSPSA-N (2s)-2,6-diaminohexanoic acid;1,3-dimethyl-7h-purine-2,6-dione Chemical compound NCCCC[C@H](N)C(O)=O.O=C1N(C)C(=O)N(C)C2=C1NC=N2 UBLVUWUKNHKCJJ-ZSCHJXSPSA-N 0.000 description 1
- FUFLCEKSBBHCMO-UHFFFAOYSA-N 11-dehydrocorticosterone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 FUFLCEKSBBHCMO-UHFFFAOYSA-N 0.000 description 1
- YREYLAVBNPACJM-UHFFFAOYSA-N 2-(tert-butylamino)-1-(2-chlorophenyl)ethanol Chemical compound CC(C)(C)NCC(O)C1=CC=CC=C1Cl YREYLAVBNPACJM-UHFFFAOYSA-N 0.000 description 1
- SMNDYUVBFMFKNZ-UHFFFAOYSA-N 2-furoic acid Chemical compound OC(=O)C1=CC=CO1 SMNDYUVBFMFKNZ-UHFFFAOYSA-N 0.000 description 1
- LSLYOANBFKQKPT-DIFFPNOSSA-N 5-[(1r)-1-hydroxy-2-[[(2r)-1-(4-hydroxyphenyl)propan-2-yl]amino]ethyl]benzene-1,3-diol Chemical compound C([C@@H](C)NC[C@H](O)C=1C=C(O)C=C(O)C=1)C1=CC=C(O)C=C1 LSLYOANBFKQKPT-DIFFPNOSSA-N 0.000 description 1
- XSFWDHONRBZVEJ-UHFFFAOYSA-N 7-[3-[[2-(3,5-dihydroxyphenyl)-2-hydroxyethyl]amino]propyl]-1,3-dimethylpurine-2,6-dione;hydron;chloride Chemical compound Cl.C1=2C(=O)N(C)C(=O)N(C)C=2N=CN1CCCNCC(O)C1=CC(O)=CC(O)=C1 XSFWDHONRBZVEJ-UHFFFAOYSA-N 0.000 description 1
- 229930003347 Atropine Natural products 0.000 description 1
- KUVIULQEHSCUHY-XYWKZLDCSA-N Beclometasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(Cl)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)COC(=O)CC)(OC(=O)CC)[C@@]1(C)C[C@@H]2O KUVIULQEHSCUHY-XYWKZLDCSA-N 0.000 description 1
- VOVIALXJUBGFJZ-KWVAZRHASA-N Budesonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H]3OC(CCC)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O VOVIALXJUBGFJZ-KWVAZRHASA-N 0.000 description 1
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
- 229930186147 Cephalosporin Natural products 0.000 description 1
- MFYSYFVPBJMHGN-ZPOLXVRWSA-N Cortisone Chemical compound O=C1CC[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 MFYSYFVPBJMHGN-ZPOLXVRWSA-N 0.000 description 1
- MFYSYFVPBJMHGN-UHFFFAOYSA-N Cortisone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)(O)C(=O)CO)C4C3CCC2=C1 MFYSYFVPBJMHGN-UHFFFAOYSA-N 0.000 description 1
- IJVCSMSMFSCRME-KBQPJGBKSA-N Dihydromorphine Chemical compound O([C@H]1[C@H](CC[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O IJVCSMSMFSCRME-KBQPJGBKSA-N 0.000 description 1
- 102000051325 Glucagon Human genes 0.000 description 1
- 108060003199 Glucagon Proteins 0.000 description 1
- RKUNBYITZUJHSG-UHFFFAOYSA-N Hyosciamin-hydrochlorid Natural products CN1C(C2)CCC1CC2OC(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-UHFFFAOYSA-N 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 108010041012 Integrin alpha4 Proteins 0.000 description 1
- HUYWAWARQUIQLE-UHFFFAOYSA-N Isoetharine Chemical compound CC(C)NC(CC)C(O)C1=CC=C(O)C(O)=C1 HUYWAWARQUIQLE-UHFFFAOYSA-N 0.000 description 1
- ZCVMWBYGMWKGHF-UHFFFAOYSA-N Ketotifene Chemical compound C1CN(C)CCC1=C1C2=CC=CC=C2CC(=O)C2=C1C=CS2 ZCVMWBYGMWKGHF-UHFFFAOYSA-N 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- QSXMZJGGEWYVCN-UHFFFAOYSA-N Pirbuterol acetate Chemical compound CC(O)=O.CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=N1 QSXMZJGGEWYVCN-UHFFFAOYSA-N 0.000 description 1
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 229960005305 adenosine Drugs 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- BNPSSFBOAGDEEL-UHFFFAOYSA-N albuterol sulfate Chemical compound OS(O)(=O)=O.CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=C1.CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=C1 BNPSSFBOAGDEEL-UHFFFAOYSA-N 0.000 description 1
- AKNNEGZIBPJZJG-UHFFFAOYSA-N alpha-noscapine Natural products CN1CCC2=CC=3OCOC=3C(OC)=C2C1C1C2=CC=C(OC)C(OC)=C2C(=O)O1 AKNNEGZIBPJZJG-UHFFFAOYSA-N 0.000 description 1
- XSDQTOBWRPYKKA-UHFFFAOYSA-N amiloride Chemical compound NC(=N)NC(=O)C1=NC(Cl)=C(N)N=C1N XSDQTOBWRPYKKA-UHFFFAOYSA-N 0.000 description 1
- 229960002576 amiloride Drugs 0.000 description 1
- 229960003556 aminophylline Drugs 0.000 description 1
- FQPFAHBPWDRTLU-UHFFFAOYSA-N aminophylline Chemical compound NCCN.O=C1N(C)C(=O)N(C)C2=C1NC=N2.O=C1N(C)C(=O)N(C)C2=C1NC=N2 FQPFAHBPWDRTLU-UHFFFAOYSA-N 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000000954 anitussive effect Effects 0.000 description 1
- 230000003266 anti-allergic effect Effects 0.000 description 1
- 230000003257 anti-anginal effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000001078 anti-cholinergic effect Effects 0.000 description 1
- 230000001387 anti-histamine Effects 0.000 description 1
- 230000002924 anti-infective effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 229940124584 antitussives Drugs 0.000 description 1
- RKUNBYITZUJHSG-SPUOUPEWSA-N atropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-SPUOUPEWSA-N 0.000 description 1
- 229960000396 atropine Drugs 0.000 description 1
- 229950000210 beclometasone dipropionate Drugs 0.000 description 1
- 229940124630 bronchodilator Drugs 0.000 description 1
- 229960004436 budesonide Drugs 0.000 description 1
- 229940124587 cephalosporin Drugs 0.000 description 1
- 150000001780 cephalosporins Chemical class 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229960003821 choline theophyllinate Drugs 0.000 description 1
- 229960004126 codeine Drugs 0.000 description 1
- 229960004544 cortisone Drugs 0.000 description 1
- 229940109248 cromoglycate Drugs 0.000 description 1
- IMZMKUWMOSJXDT-UHFFFAOYSA-N cromoglycic acid Chemical compound O1C(C(O)=O)=CC(=O)C2=C1C=CC=C2OCC(O)COC1=CC=CC2=C1C(=O)C=C(C(O)=O)O2 IMZMKUWMOSJXDT-UHFFFAOYSA-N 0.000 description 1
- KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 description 1
- 229940039227 diagnostic agent Drugs 0.000 description 1
- 239000000032 diagnostic agent Substances 0.000 description 1
- HSUGRBWQSSZJOP-RTWAWAEBSA-N diltiazem Chemical compound C1=CC(OC)=CC=C1[C@H]1[C@@H](OC(C)=O)C(=O)N(CCN(C)C)C2=CC=CC=C2S1 HSUGRBWQSSZJOP-RTWAWAEBSA-N 0.000 description 1
- 229960004166 diltiazem Drugs 0.000 description 1
- PCHPORCSPXIHLZ-UHFFFAOYSA-N diphenhydramine hydrochloride Chemical compound [Cl-].C=1C=CC=CC=1C(OCC[NH+](C)C)C1=CC=CC=C1 PCHPORCSPXIHLZ-UHFFFAOYSA-N 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 230000001882 diuretic effect Effects 0.000 description 1
- DLNKOYKMWOXYQA-UHFFFAOYSA-N dl-pseudophenylpropanolamine Natural products CC(N)C(O)C1=CC=CC=C1 DLNKOYKMWOXYQA-UHFFFAOYSA-N 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 229960002179 ephedrine Drugs 0.000 description 1
- OFKDAAIKGIBASY-VFGNJEKYSA-N ergotamine Chemical compound C([C@H]1C(=O)N2CCC[C@H]2[C@]2(O)O[C@@](C(N21)=O)(C)NC(=O)[C@H]1CN([C@H]2C(C3=CC=CC4=NC=C([C]34)C2)=C1)C)C1=CC=CC=C1 OFKDAAIKGIBASY-VFGNJEKYSA-N 0.000 description 1
- 229960004943 ergotamine Drugs 0.000 description 1
- XCGSFFUVFURLIX-UHFFFAOYSA-N ergotaminine Natural products C1=C(C=2C=CC=C3NC=C(C=23)C2)C2N(C)CC1C(=O)NC(C(N12)=O)(C)OC1(O)C1CCCN1C(=O)C2CC1=CC=CC=C1 XCGSFFUVFURLIX-UHFFFAOYSA-N 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 229960001022 fenoterol Drugs 0.000 description 1
- PJMPHNIQZUBGLI-UHFFFAOYSA-N fentanyl Chemical compound C=1C=CC=CC=1N(C(=O)CC)C(CC1)CCN1CCC1=CC=CC=C1 PJMPHNIQZUBGLI-UHFFFAOYSA-N 0.000 description 1
- 229960002428 fentanyl Drugs 0.000 description 1
- 229960000676 flunisolide Drugs 0.000 description 1
- 229960000289 fluticasone propionate Drugs 0.000 description 1
- WMWTYOKRWGGJOA-CENSZEJFSA-N fluticasone propionate Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@@H](C)[C@@](C(=O)SCF)(OC(=O)CC)[C@@]2(C)C[C@@H]1O WMWTYOKRWGGJOA-CENSZEJFSA-N 0.000 description 1
- 229960002848 formoterol Drugs 0.000 description 1
- BPZSYCZIITTYBL-UHFFFAOYSA-N formoterol Chemical compound C1=CC(OC)=CC=C1CC(C)NCC(O)C1=CC=C(O)C(NC=O)=C1 BPZSYCZIITTYBL-UHFFFAOYSA-N 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 description 1
- 229960004666 glucagon Drugs 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 description 1
- 229960000890 hydrocortisone Drugs 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 229960001888 ipratropium Drugs 0.000 description 1
- OEXHQOGQTVQTAT-JRNQLAHRSA-N ipratropium Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)[N@@+]2(C)C(C)C)C(=O)C(CO)C1=CC=CC=C1 OEXHQOGQTVQTAT-JRNQLAHRSA-N 0.000 description 1
- 229960001268 isoetarine Drugs 0.000 description 1
- 229960001317 isoprenaline Drugs 0.000 description 1
- 229960004958 ketotifen Drugs 0.000 description 1
- 229960001869 methapyrilene Drugs 0.000 description 1
- HNJJXZKZRAWDPF-UHFFFAOYSA-N methapyrilene Chemical compound C=1C=CC=NC=1N(CCN(C)C)CC1=CC=CS1 HNJJXZKZRAWDPF-UHFFFAOYSA-N 0.000 description 1
- 229960005181 morphine Drugs 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- PLPRGLOFPNJOTN-UHFFFAOYSA-N narcotine Natural products COc1ccc2C(OC(=O)c2c1OC)C3Cc4c(CN3C)cc5OCOc5c4OC PLPRGLOFPNJOTN-UHFFFAOYSA-N 0.000 description 1
- 229960004398 nedocromil Drugs 0.000 description 1
- RQTOOFIXOKYGAN-UHFFFAOYSA-N nedocromil Chemical compound CCN1C(C(O)=O)=CC(=O)C2=C1C(CCC)=C1OC(C(O)=O)=CC(=O)C1=C2 RQTOOFIXOKYGAN-UHFFFAOYSA-N 0.000 description 1
- 229960004708 noscapine Drugs 0.000 description 1
- 229960000797 oxitropium Drugs 0.000 description 1
- NVOYVOBDTVTBDX-PMEUIYRNSA-N oxitropium Chemical compound CC[N+]1(C)[C@H]2C[C@@H](C[C@@H]1[C@H]1O[C@@H]21)OC(=O)[C@H](CO)C1=CC=CC=C1 NVOYVOBDTVTBDX-PMEUIYRNSA-N 0.000 description 1
- RLANKEDHRWMNRO-UHFFFAOYSA-M oxtriphylline Chemical compound C[N+](C)(C)CCO.O=C1N(C)C(=O)N(C)C2=C1[N-]C=N2 RLANKEDHRWMNRO-UHFFFAOYSA-M 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 150000002960 penicillins Chemical class 0.000 description 1
- 229960004448 pentamidine Drugs 0.000 description 1
- XDRYMKDFEDOLFX-UHFFFAOYSA-N pentamidine Chemical compound C1=CC(C(=N)N)=CC=C1OCCCCCOC1=CC=C(C(N)=N)C=C1 XDRYMKDFEDOLFX-UHFFFAOYSA-N 0.000 description 1
- 229960001802 phenylephrine Drugs 0.000 description 1
- SONNWYBIRXJNDC-VIFPVBQESA-N phenylephrine Chemical compound CNC[C@H](O)C1=CC=CC(O)=C1 SONNWYBIRXJNDC-VIFPVBQESA-N 0.000 description 1
- 229960000395 phenylpropanolamine Drugs 0.000 description 1
- DLNKOYKMWOXYQA-APPZFPTMSA-N phenylpropanolamine Chemical compound C[C@@H](N)[C@H](O)C1=CC=CC=C1 DLNKOYKMWOXYQA-APPZFPTMSA-N 0.000 description 1
- 229960004994 pirbuterol acetate Drugs 0.000 description 1
- 229960005205 prednisolone Drugs 0.000 description 1
- OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- MIXMJCQRHVAJIO-TZHJZOAOSA-N qk4dys664x Chemical compound O.C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O.C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O MIXMJCQRHVAJIO-TZHJZOAOSA-N 0.000 description 1
- 229960000261 reproterol hydrochloride Drugs 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 229960001457 rimiterol Drugs 0.000 description 1
- IYMMESGOJVNCKV-SKDRFNHKSA-N rimiterol Chemical compound C([C@@H]1[C@@H](O)C=2C=C(O)C(O)=CC=2)CCCN1 IYMMESGOJVNCKV-SKDRFNHKSA-N 0.000 description 1
- 229950004432 rofleponide Drugs 0.000 description 1
- IXTCZMJQGGONPY-XJAYAHQCSA-N rofleponide Chemical compound C1([C@@H](F)C2)=CC(=O)CC[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@H]3O[C@@H](CCC)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O IXTCZMJQGGONPY-XJAYAHQCSA-N 0.000 description 1
- 229960004017 salmeterol Drugs 0.000 description 1
- 229960005018 salmeterol xinafoate Drugs 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- KFVSLSTULZVNPG-UHFFFAOYSA-N terbutaline sulfate Chemical compound [O-]S([O-])(=O)=O.CC(C)(C)[NH2+]CC(O)C1=CC(O)=CC(O)=C1.CC(C)(C)[NH2+]CC(O)C1=CC(O)=CC(O)=C1 KFVSLSTULZVNPG-UHFFFAOYSA-N 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 229940040944 tetracyclines Drugs 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 229960000278 theophylline Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- LERNTVKEWCAPOY-DZZGSBJMSA-N tiotropium Chemical compound O([C@H]1C[C@@H]2[N+]([C@H](C1)[C@@H]1[C@H]2O1)(C)C)C(=O)C(O)(C=1SC=CC=1)C1=CC=CS1 LERNTVKEWCAPOY-DZZGSBJMSA-N 0.000 description 1
- 229940110309 tiotropium Drugs 0.000 description 1
- 229960002117 triamcinolone acetonide Drugs 0.000 description 1
- YNDXUCZADRHECN-JNQJZLCISA-N triamcinolone acetonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O YNDXUCZADRHECN-JNQJZLCISA-N 0.000 description 1
- 229960000859 tulobuterol Drugs 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 229940075420 xanthine Drugs 0.000 description 1
- ARAIBEBZBOPLMB-UFGQHTETSA-N zanamivir Chemical compound CC(=O)N[C@@H]1[C@@H](N=C(N)N)C=C(C(O)=O)O[C@H]1[C@H](O)[C@H](O)CO ARAIBEBZBOPLMB-UFGQHTETSA-N 0.000 description 1
- 229960001028 zanamivir Drugs 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M15/00—Inhalators
- A61M15/0028—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up
- A61M15/0045—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up using multiple prepacked dosages on a same carrier, e.g. blisters
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M15/00—Inhalators
- A61M15/0001—Details of inhalators; Constructional features thereof
- A61M15/0021—Mouthpieces therefor
- A61M15/0025—Mouthpieces therefor with caps
- A61M15/0026—Hinged caps
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M15/00—Inhalators
- A61M15/0028—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up
- A61M15/003—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up using capsules, e.g. to be perforated or broken-up
- A61M15/0031—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up using capsules, e.g. to be perforated or broken-up by bursting or breaking the package, i.e. without cutting or piercing
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M15/00—Inhalators
- A61M15/0028—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up
- A61M15/003—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up using capsules, e.g. to be perforated or broken-up
- A61M15/0043—Non-destructive separation of the package, e.g. peeling
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M15/00—Inhalators
- A61M15/0028—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up
- A61M15/0045—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up using multiple prepacked dosages on a same carrier, e.g. blisters
- A61M15/0046—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up using multiple prepacked dosages on a same carrier, e.g. blisters characterized by the type of carrier
- A61M15/0048—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up using multiple prepacked dosages on a same carrier, e.g. blisters characterized by the type of carrier the dosages being arranged in a plane, e.g. on diskettes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M15/00—Inhalators
- A61M15/0065—Inhalators with dosage or measuring devices
- A61M15/0068—Indicating or counting the number of dispensed doses or of remaining doses
- A61M15/007—Mechanical counters
- A61M15/0071—Mechanical counters having a display or indicator
- A61M15/0075—Mechanical counters having a display or indicator on a disc
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M2202/00—Special media to be introduced, removed or treated
- A61M2202/06—Solids
- A61M2202/064—Powder
Definitions
- This invention relates to inhalers and in particular to inhalers for use with powered medicaments.
- inhalers There are many types of inhalers that can provide delivered metered doses. The majority of inhalers of this kind are designed to provide multiple doses. It is however known that inhalers of this kind can also be used to provide a single dose.
- inhalers In situations where a metered dose is to be dispensed it is important that the inhaler always dispenses the exact dose. There is also a problem with inhalers of this kind if there is a tendency to allow unintentional additional dosing. Inhalers need to be small, compact, easy to use and yet not too expensive. The inhalers also need to satisfy safety criteria set down by appropriate standards.
- WO 02/24263 discloses an inhalation device for delivering unit doses of powdered medicament having a removably mounted cartridge with a plurality of compartments each for containing a discrete unit dose and a sealing layer for closing the compartments, and a separator for removing the sealing layer from a respective compartment to open an air flow passageway defined by the compartment and the separator.
- the document WO 02/24263 is state of the art according to Art. 54(3) EPC.
- an inhaler for delivering metered doses of powdered medicament, the inhaler having a plurality of compartments spaced in an annular array and each containing a metered dose of the medicament, a lever to displace the compartments one by one into line with an inhalation aperture that constitutes a mouthpiece, each compartment including radially inner and outer edges, the plurality of compartments being closed by a sealing layer, characterised in that the inhaler has a mechanism adapted to lift the inner and outer edges of the sealing layer off the radially inner and outer edges of each compartment one by one as it is indexed to align with the inhalation aperture to open an air passageway defined by the compartment and the sealing layer so that, in use, on inhalation through the mouthpiece, air flow in the air flow passageway picks up and entrains the powder in the compartment to be drawn with the air out of the inhaler through the mouthpiece.
- an inhaler 10 comprises a disposable medicament cartridge 50 that is located in an inhaler body 11 that includes an upper body 12, lower body 13 that fit together to support a drive cam 18 and lever 30 and define a recess 14 into which the cartridge 50 fits.
- the body 11 is closed by a lid 15 that is hinged to one side 16 of the body 11.
- the upper surface of the lid supports a window 100, air entry inlet 19 and air entry indicator 110 and a one way valve 112.
- the inhaler 10 is substantially circular in plan and has a mouthpiece 26 having an inhalation aperture 27 positioned in the body periphery on one side with the displacement lever 30 located on that side to be displaceable relative to the body 11 between the open position shown in Figure 2a to the closed position in which the lever 30 covers the mouthpiece 26 as shown in Figure 2b .
- the cartridge 50 is shown in greater detail in Figure 4 and comprises a multi-layered annular disc assembly that is located between upper and lower covers 52, 51 that clip together as shown in Figure 10 .
- the upper cover 52 has an air inlet aperture 45 that communicates with the disc assembly to define an air passageway that exits the cartridge via slot 29 on the periphery of the lower cover 51.
- the disc assembly includes a cartridge base 55 that is of disc shape with a central aperture 56.
- the cartridge base 55 supports a base foil 60 that has a central aperture 61 and contains ten recessed compartments 70 spaced around the periphery of the base foil 60. The compartments are equally spaced except that there is a wider gap between the first 64 and the last 65 compartments.
- the base 55 is formed with recesses that correspond to the compartments 70.
- the base foil 60 is covered first by a perforated layer 80 which is in turn covered by a lidding foil layer 90.
- Both the perforated layer and lidding foil 80 and 90 have internal apertures 81 and 91.
- the apertures 56, 61, 81 in the cartridge base 55, base foil 60 and perforated layer 80 include a cut-out 57, 62 and 82 that is radically aligned with a cut-out 58, 63, and 83 in the outer periphery.
- the lidding foil 90 is securely bonded to the perforated layer 80 which is attached to the base foil 60 to seal the compartments 70 once filled with medicament powder.
- the cartridge 50 is designed to hold a plurality of metered doses of powdered medicament in separate sealed compartments 70 and the operation of the lever 30 displaces the drive cam 18 which rotates components of the cartridge 50 to expose individual doses to the air passageway that is in communication with the mouthpiece 26.
- the cartridge 50 includes openers 86, 87 located in the lower cover 51 that operates to expose a single dose by unsealing each compartment 70 so that when the user inhales through the mouthpiece 26 air is drawn through an aperture in the lid 15 of the inhaler 10 through the inlet aperture of the cartridge, across the unsealed compartment 70 to pick up the powder in the compartment 70 for delivery to the mouthpiece 26 via the outlet slot 29.
- the cartridge 50 can be disposed of and be replaced by a new cartridge when all or part of the compartments 70 of the powered medicament have been emptied.
- the inhaler is in consequence reusable.
- the cartridge may be removed or reinserted as required.
- the underside of the periphery of the cartridge base 55 is provided with a plurality of equally spaced cutouts 53, that are adapted to be engaged by the drive cam 18 driven by the lever 30 to cause the cartridge base 55, base foil 60, perforated layer 80, lidding foil 90 and upper cover 52 to be rotated through a small angle when the lever 30 is displaced in the anti-clockwise direction.
- the upper cover 52 is also rotated by the drive cam 18 through a small angle when the lever 30 is displaced in the clockwise direction.
- compartments 70 can be positioned on the base foil 60 and the cartridge base 55 can include as many peripheral cutouts as are necessary to ensure that each compartment is indexed to the required position by displacement of the lever 30.
- the base foil 60 is positioned axially aligned on top of the cartridge base 55.
- the lower cover 51 has an arcuate slot 9 through which the drive cam 18 extends to engage the cartridge base.
- the lower cover 51 of the cartridge 50 has a central upstanding circular spigot 84 that includes an internal upstanding ring 85.
- a pair of radially aligned wedges 87 and 86 extend outwardly and inwardly from the spigot 84 and inner wall of the lower cover 51.
- the laminated cartridge assembly is lowered into the lower cover 51 with the wedge shaped openers 87, 86 clearing the inner and outer slots 57, 58, 62, 63, 82 & 83 on the central apertures and outer peripheries of the base, base foil and perforated layers respectively.
- the lidding foil layer 90 does not have slots on the inner and outer peripheries which means that the foil rests on the wedges 86, 87.
- the cartridge 50 is completed by location of the upper cover 52 into locked engagement with the lower cover 51.
- the upper cover 52 has a peripheral downwardly extending skirt 49 with a rectangular cut-out 48 into which a lug 108 on the end of the drive cam 18 locates so movement of the drive cam 18 causes a rotational movement of the upper cover 52.
- the upper cover 52 has a central tapered boss 95 that clips into the ring 85 in the lower cover 51.
- a downwardly extending annular flange 96 fits against the exterior of the ring 85 allowing the upper cover 52 to oscillate relative to the lower cover 51.
- the upper surface of the upper cover 52 includes a viewing aperture 44 and an air inlet aperture 45.
- a finger tab 46 extends down from the upper surface of the cover to provide ease of removal of the cartridge 50 from the inhaler body.
- the underside of the upper cover 52 also has an elongate downwardly extending bar 47 that, in use, engages the top of the lidding foil 90 to push back the lidding foil onto the perforated layer 80, base foil 60 and base 55 after the contents of a compartment have been ejected.
- the bar 47 thus partially reseals the compartment.
- Figure 3 shows how the cartridge 50 can be lowered into the inhaler body 11.
- the cartridge 50 is gripped by the finger tab 46 and lowered into the recess 14 of the inhaler body 11 with outlet slot 29 aligned with the mouthpiece 26.
- the shape of the cartridge 50 is such that it can only be positioned in the inhaler in the correct position.
- the lever that drives the cartridge base 55 to rotate relative to the lower cover 51 of the cartridge 50 also has the effect of causing the upper cover 52 to oscillate on the lower cover 51 by contact between the lug 108 on the drive cam 18 and the cut-out 48 in the upper cover 52.
- the connection between the lever 30 and drive cam 18 introduces a small degree of free play or neutral movement.
- the role of the wedge shaped openers 86, 87 is illustrated with particular reference to Figures 10 and 11 .
- the disc assembly sits in the lower cover 51 with the wedge shaped openers 86, 87 resting against the underside of the lidding foil layer 90.
- the inclined ramp on the upper surface of the openers 86, 87 has the effect of partially lifting the lidding foil 90 at the inner and outer sections from the top of the perforated layer 80 thereby exposing the powder within the compartment 70.
- the openers can either be positioned in a leading, central or trailing position in relation to the medicament compartment 70 on the assembly and as the disc continues to rotate, the openers lift the inner and outer sections of the lidding foil to expose the contents for removal upon inhalation and then allow the lidding foil to fall back into position against the perforated layer 80 thereby re-closing the compartment 70.
- the trailing bar 47 on the underside of the upper cover 52 then pushes the foil back against the base foil to partially reseal the compartment.
- the lid 15 of the inhaler is shown in greater detail in Figures 2 , 12 and 13 .
- the lid has a circular shaped clear cover 100 with a viewing tab 101 on one side and an arcuate window 102 on the opposite side.
- the circular shaped clear cover 100 is obscured except for an area 103.
- the underside of the lid has a central spigot 104 which supports a flow indicator 110 and a flap valve 112. As air is drawn into the inhaler through the air inlet 19, the flexible flap valve 112 pivots open as shown in detail B. Any attempt to blow air back through the inhaler is prevented by the flap valve 112 moving to the closed position shown in detail A.
- the flow indicator 110 is in the form of an arcuate flag 113 that has downward projections 114, that reside in grooves 116 in the underside of the lid.
- the flag 113 As air is drawn into the inhaler 10 it causes the flag 113 to move in the grooves 116 and to rise up a ramp to assume a visible position through the area 103 of the window 100. The ramp tends to hold the flag 113 in the operative position after inhalation.
- the lever 30 is indexed to the closed position, the oscillating movement of the top of the cartridge 50 causes arcuate cut-outs 117 and 118 in the top 52 of the cartridge to engage the projections 114 to return the flag 113 to the inoperative and less visible position.
- the incoming air current is sufficient to drive the flag 113 to the operative position.
- the airflow is such that when the user inhales on the mouthpiece 26 air is drawn into the inhaler 10 via the air inlet 19 around the underside of the window 100 into the inhaler to move the flag 113 to the position shown in Figure 13b .
- the air flows in to the inhaler displacing the one way valve 112 and into the cartridge 50.
- the air flows through the air inlet 45 at the top of the cartridge and out under the lidding foil that has been prized upwardly by the openers 86, 87, through the perforated layer 80 across the top of the compartment 70 and out through the radially outer section of the compartment through the perforated layer 80 and the inhalation aperture 27 and mouth piece 26.
- the air current is such that it causes turbulence causing the powder to be drawn through the perforated layer 80 to be entrained in the air for expulsion.
- the perforated layer 80 has the role of preventing escape of powder without the air current so thus, if for some reason, the lidding foil 90 is removed from the compartment by accident the perforated layer 80 prevents escape of the powder and only allows powder escape when it is entrained in an air current.
- the perforations in the layer 80 also assist to control the particle size of the released medicament.
- the lid also includes the small viewing tab 101 that exposes through magnification an arcuate line of numbering that would be positioned on the lidding foil 90 and exposed through the hole 44 in the upper cover 52.
- the numbering reflects the number of recesses 70 with unused doses so that the user of the inhaler can know how many doses remain in the cartridge.
- the inhaler 10 also includes a number of other features that reduce inadvertent additional dosage and reduce the likelihood of accidental displacement of the medicament. It is only on a full displacement of the lever 30 to the right as shown in Figure 3 that opens the next dose and indexes the cartridge so the dose is positioned in line with the airflow passageway.
- the lever is connected to an arcuate band the drive cam 18 that locates on the inner surface of the body 11. The connection between the drive lever 30 and drive cam 18 introduces a small degree of free play or neutral movement.
- the lever is coupled to the drive cam having an aperture 109 so that only full displacement of the lever to the right as shown in Figure 4 moves the aperture 109 in the drive cam 18 into correct alignment with the aperture 27 of the mouthpiece 26 to open the air passageway. When the lever returns to the left or closed position the drive cam moves to close off the mouthpiece 26.
- the lever 30 that closes off the airflow passageway and does not open this passageway until the lever has again been displaced fully to the right.
- the openers 86, 87 lift the lidding foil 90 from the perforated layer 80 to expose the radially inner and outer sections of recessed compartment 70.
- the foil 90 has been lifted from the radially inner and outer sections of the compartment 70 to open the air passageway.
- the air passageway is open to the mouthpiece 26 allowing inhalation. If the lever is closed i.e. returned to its original position to the left without taking the dose that dose will then be lost because it will be indexed into an inoperative position when the lever has moved again. Thus reducing the possibility of unintentional additional dosing.
- the cover 52 that is positioned over the foils 60, 80 and 90 protects doses that are not used from escape into the inhaler so that once the cartridge is discarded any residual medicament is discarded with the cartridge. Because the openers 86, 87 only lifts the lidding foil 90 off the perforated layer 80 an unadministered dose becomes effectively sealed in its compartment 70 as it is indexed past the openers which allows the lidding foil to return to its former position with the bar 47 closing off the compartment 70.
- the flap 112 operates as a one-way valve to ensure that exhalation does not have any effect on the medicament.
- the valve virtually prevents or at least minimises the amount of air that can be blown into the device so that exhalation does not dislodge or disturb a readied dose or for that matter disturb a dose that has not been administered.
- the one way valve 112 closes the air flow pathway exit to minimise the possibility of air flow over the unadministered dose.
- the shape of the cutouts in the periphery of the base is such that when the last dose has been dispensed the lever cannot further rotate the disc so that the user becomes aware that the cartridge is empty and can thus replace the cartridge.
- FIGs 15 to 17 illustrate a second embodiment that utilises a different cartridge which is shown in Figure 15 .
- the cartridge 150 has a slit top foil layer 190 provided with radial slits 192 that define segments that correspond to the position of each compartment.
- the top foil layer 190 has a central aperture 191 and is bonded to the lower foil 160 to seal off the compartments 170.
- a circular assembly 180 of flip top members 181 is bonded to the top foil 190.
- the assembly 180 comprises a plastics moulding in the form of a plurality of radially extending flip top members 181 that are interconnected by circumferentially extending webs 182.
- Each flip top member 181 comprises a radially outer arm 184 that is joined to a V-shaped inner arm 185 by the webs 182 that interconnect that flip top member 181 to the adjacent flip top members.
- the underside of both the radially outer and inner arms include downwardly projecting triangular shaped lugs 187 and 188.
- the bonding of the assembly 180 to the top foil 190 means that each segment includes a segmentally shaped piece of foil with the skeletal framework of the flip top members 181 transcribing the inner and outer circumferential edges 193 and 194 as well as the radial edges of the segment. Because the assembly 180 is bonded to the top foil 190, rotation of the disc base 151 causes rotation of the assembly 180, top foil 190 and lower foil 160 in unison relative to the cover 195.
- the assembly of the disc base 151, two foil layers 160 and 190 and flip top assembly 180 is then covered by a plastics cover 195 that has a central aperture 196 and a downwardly extending annular skirt 197 that covers the components.
- An arcuate cutout 198 is provided in the periphery of the skirt 197 of the cover 195 through which a lever (not shown), similar to the first embodiment, can extend to engage the disc base 151.
- the rotation of the disc base 151 and foil layers 160 and 190 and flip top assembly 180 relative to the cover 195 is illustrated in Figure 16 .
- An arcuate cutout 199 is provided in the periphery of the skirt 197 of the cover 195 which, prevents the base rotating in the wrong direction by engaging the disc base 151.
- Displacement of the lever rotates the disc base 151 causing the inner and outer lugs 187, 188 on the flip top member 181 to ride up on radial projections on the base of the inhaler (not shown) to cause the arms 184, 185 of the flip top members 181 to flex upwardly as shown in Figure 17 about the central line or webs 182.
- Upward flexing of the flip top members 181 lifts the top foil 190 from the radially inner and outer edges of the compartments 170 causing an air passageway to form between the centre of the cartridge 150, the lifted inner flip top arm 184 the compartment 170 and the lifted outer flip top arm 185. In this way the airflow passageway is defined by the top foil 190, the flip top member 181 and the compartment 170.
- the cover 195 of the cartridge has inclined up standing portions 175 and 176 that are positioned to accommodate the flip top member 181 in the elevated position as shown in Figure 17 .
- the undersurface of the cover 195 forces the previously opened flip top members 181 down to the horizontal position, shown around the remainder of the periphery of the flip top assembly 180 in Figure 15 .
- the radial slits 192 in the top foil 190 facilitate the upward movement of the flip top members 181 relative to the remainder of the foil 190.
- the flip top assembly 180 has a dual role of displacing the top foil 190 layer from the lower foil 160 and thus exposing each compartment 170 whilst at the same time forming a framework for an air passageway that flows from the aperture in the top of the lid of the inhaler down through the centre of the inhaler and along the radial arms 184, 185 to pass through the end of the radial outer arm 185 and through the mouthpiece in the periphery of the body.
- the flip top members 181 lift the top foil 190 off the lower foil 160 and the radial edges of the compartment and the skeletal structure of the members 181 coupled with the foil surfaces provides the air passageway so that the user inhales through the mouthpiece drawing air down and into the inhaler and through the passageway.
- the air current picks up the powder in the exposed recess 170.
- the powder is then entrained in the air to leave the inhaler via the mouthpiece.
- the disc base 251 and lower foil 260 are provided with radially inner and outer cutouts 252, 253, 262, 263 in the gap 268 between the first and last compartment 264, 265.
- the cut-outs 252, 253, 262, 263 accommodate a disc opener 220 in the form of a bracket having a flat base 221 terminating an upstanding posts 222, 223, 224, 225 at either end with the posts having inturned downwardly extending flanges 226.
- the posts and flanges 226 are positioned on the radially outer and radially inner end of the opener 220 and allow the opener to clip against the underside of the disc base 251 with the flat base 221 in parallel sliding contact with the underside of disc base 251 and the flanges 226 extending across the lower foil 260 surface but beneath the upper foil 290.
- the disc opener 220 is located in the cover 250 of the cartridge in a manner that it cannot rotate with the disc base 251 so that as the disc base is rotated the leading edges of the flanges 226 have the effect of lifting up the radially inner and outer edges of the top foil 290 on the adjacent compartment 270.
- the radially inner and radially outer edges of the top foil 290 are lifted clear of the compartment 270 and the air passageway is defined by the compartment base and the top foil 290 that has been raised at least adjacent the radially outer and radially inner edges of the compartment by the disc opening flanges 226.
- the top foil 290 lifts off a single compartment 270 the radially outer 271 and radially inner edges 272 of each compartment 270 are at a position lower than the centre of the compartment 273 so that the disc opener flanges 226 only have to lift the radially inner 291 and radial outer 292 edges of the top foil level with the centre 293. It is for this reason that the top foil 290 is illustrated with what appear to be concentric rings.
- the central ring 293 allows the radially inner and radially outer sections of the top foil 290 to lift into the open position. This arrangement provides a narrow passageway whereby the central portion of the top foil 290 remains above the recessed compartment 270 and the air current to ensure that the air current is in close proximity to the powdered medicament.
- the cover 295 of the disc 250 is provided with a raised inclined section 296 over the position of the disc opener 220 to accommodate the upstanding posts and flanges 226.
- the inhaler is reusable, whilst the empty cartridges are discarded.
- Cartridges can be supplied with a range of dose number, medicament type and volume.
- Full and partially full cartridges can be loaded into and removed from the inhaler as required - either well before a dose is required or just prior to use.
- the dose is opened and prepared for inhalation by simply sliding the indexing lever.
- the access to the mouthpiece is opened or closed by simply sliding the indexing lever.
- the inhaler via the cartridge has a "doses remaining" indicator.
- the inhaler has an indicator to indicate correct dosage received.
- the cartridge covers and foils protect the user from residues in opened compartments of the cartridge.
- the inhaler comprises an inhaler body and disposable cartridge it is understood that in a simple form the inhaler may simply be like the cartridge that is without the external body.
- the cartridge would include a mechanism to displace the compartments and cause opening of each compartment when it is aligned with an outlet aperture that would serve as the mouthpiece.
- the inhaler may be used to provide medications selected from the following therapy areas: antiinfluenza, analgesic, anti-anginal preparation, antiallergic, anti-infective, anticancer, antihistamine, anti-inflammatory, antitussive, bronchodilator, cortiscosteroid, diuretic, anticholinergic, hormone, xanthine, osteoporosis, hypertension, therapeutic protein or peptide, vaccine, diagnostic agent or gene therapy agent.
- medications selected from the following therapy areas: antiinfluenza, analgesic, anti-anginal preparation, antiallergic, anti-infective, anticancer, antihistamine, anti-inflammatory, antitussive, bronchodilator, cortiscosteroid, diuretic, anticholinergic, hormone, xanthine, osteoporosis, hypertension, therapeutic protein or peptide, vaccine, diagnostic agent or gene therapy agent.
- the inhaler may be used to provide medications selected from the following group: zanamivir, codeine, dihydromorphine, ergotamine, fentanyl, morphine, diltiazem, cromoglycate, ketotifen, nedocromil, cephalosporins, penicillins, streptomycin, sulphonamides, tetracyclines, pentamidine, methapyrilene, beclomethasone dipropionate, fluticasone propionate, flunisolide, budesonide, rofleponide, mometsasone furoate, triamcinolone acetonide, noscapine, albuterol sulphate, salmeterol xinafoate, salmeterol, ephedrine, adrenaline, fenoterol, formoterol, isoprenaline, metaproterenol, phenylephrine, phenylpropanolamine
Description
- This invention relates to inhalers and in particular to inhalers for use with powered medicaments.
- There are many types of inhalers that can provide delivered metered doses. The majority of inhalers of this kind are designed to provide multiple doses. It is however known that inhalers of this kind can also be used to provide a single dose.
- In situations where a metered dose is to be dispensed it is important that the inhaler always dispenses the exact dose. There is also a problem with inhalers of this kind if there is a tendency to allow unintentional additional dosing. Inhalers need to be small, compact, easy to use and yet not too expensive. The inhalers also need to satisfy safety criteria set down by appropriate standards.
- It is these issues that have brought about the present invention.
- One known device is shown in
WO 02/24263 WO 02/24263 - The documents
GB 2 264 237 FR 2 662 936 US 6 065 472 disclose other inhalation devices for delivering unit doses of powdered medicament. - In accordance with the present invention there is provided an inhaler for delivering metered doses of powdered medicament, the inhaler having a plurality of compartments spaced in an annular array and each containing a metered dose of the medicament, a lever to displace the compartments one by one into line with an inhalation aperture that constitutes a mouthpiece, each compartment including radially inner and outer edges, the plurality of compartments being closed by a sealing layer, characterised in that the inhaler has a mechanism adapted to lift the inner and outer edges of the sealing layer off the radially inner and outer edges of each compartment one by one as it is indexed to align with the inhalation aperture to open an air passageway defined by the compartment and the sealing layer so that, in use, on inhalation through the mouthpiece, air flow in the air flow passageway picks up and entrains the powder in the compartment to be drawn with the air out of the inhaler through the mouthpiece.
- Further features of the invention are specified in the subsidiary claims.
- Embodiments of the present invention will now be described by way of example only in which:
-
Figure 1 is an exploded view perspective view of an inhaler in accordance with a first embodiment of the invention, -
Figure 2A & 2B are perspective views of the inhaler, -
Figure 3 is an exploded perspective view of the inhaler that shows a lid of the inhaler in an open position with a cartridge outside the inhaler, -
Figure 4 is an exploded perspective view of the cartridge, -
Figure 5 is a perspective view of a lower cover of the cartridge, -
Figure 6 is a perspective view of the underside of a base of the cartridge, -
Figure 7 is a perspective view of the underside of a upper cover of the cartridge, -
Figures 8a and 8b are perspective views of the assembled cartridge viewed from the top, -
Figure 9 is a plan view of the cartridge, -
Figure 10 is a cross sectional view taken along the lines A-A ofFigure 9 , -
Figure 11 is a perspective view of the cartridge with part cutaway showing an open compartment, -
Figure 12 is a perspective view with part cut away of the assembled inhaler showing the air passageway, -
Figures 13a and 13b are perspective views of the top of the inhaler with part of a cover cut away, and -
Figures 14 are perspective views of the underside of the lid of the inhaler, -
Figure 15 is an exploded perspective view of a cartridge for an inhaler in accordance with a second embodiment of the invention, -
Figure 16 is a perspective view of an upper cover of the cartridge ofFigure 15 , -
Figure 17 is a cross sectional view taken along the lines 8-8 ofFigure 16 , -
Figure 18 is an exploded perspective view of a cartridge for an inhaler in accordance with a third embodiment of the invention, and -
Figure 19 is an enlarged perspective view of the mouth of the cartridge shown inFigure 18 . - As shown in the exploded view of
Figure 1 aninhaler 10 comprises adisposable medicament cartridge 50 that is located in an inhaler body 11 that includes anupper body 12,lower body 13 that fit together to support adrive cam 18 andlever 30 and define arecess 14 into which thecartridge 50 fits. The body 11 is closed by alid 15 that is hinged to oneside 16 of the body 11. The upper surface of the lid supports awindow 100,air entry inlet 19 andair entry indicator 110 and a oneway valve 112. - As shown in
Figure 2 , theinhaler 10 is substantially circular in plan and has amouthpiece 26 having aninhalation aperture 27 positioned in the body periphery on one side with thedisplacement lever 30 located on that side to be displaceable relative to the body 11 between the open position shown inFigure 2a to the closed position in which thelever 30 covers themouthpiece 26 as shown inFigure 2b . - The
cartridge 50 is shown in greater detail inFigure 4 and comprises a multi-layered annular disc assembly that is located between upper andlower covers Figure 10 . Theupper cover 52 has anair inlet aperture 45 that communicates with the disc assembly to define an air passageway that exits the cartridge viaslot 29 on the periphery of thelower cover 51. The disc assembly includes acartridge base 55 that is of disc shape with acentral aperture 56. Thecartridge base 55 supports abase foil 60 that has acentral aperture 61 and contains ten recessedcompartments 70 spaced around the periphery of thebase foil 60. The compartments are equally spaced except that there is a wider gap between the first 64 and the last 65 compartments. Thebase 55 is formed with recesses that correspond to thecompartments 70. - The
base foil 60 is covered first by aperforated layer 80 which is in turn covered by alidding foil layer 90. Both the perforated layer andlidding foil internal apertures apertures cartridge base 55,base foil 60 andperforated layer 80 include a cut-out 57, 62 and 82 that is radically aligned with a cut-out 58, 63, and 83 in the outer periphery. Thelidding foil 90 is securely bonded to theperforated layer 80 which is attached to thebase foil 60 to seal thecompartments 70 once filled with medicament powder. - The
cartridge 50 is designed to hold a plurality of metered doses of powdered medicament in separate sealedcompartments 70 and the operation of thelever 30 displaces thedrive cam 18 which rotates components of thecartridge 50 to expose individual doses to the air passageway that is in communication with themouthpiece 26. As shown inFigure 5 , thecartridge 50 includesopeners lower cover 51 that operates to expose a single dose by unsealing eachcompartment 70 so that when the user inhales through themouthpiece 26 air is drawn through an aperture in thelid 15 of theinhaler 10 through the inlet aperture of the cartridge, across theunsealed compartment 70 to pick up the powder in thecompartment 70 for delivery to themouthpiece 26 via theoutlet slot 29. Thecartridge 50 can be disposed of and be replaced by a new cartridge when all or part of thecompartments 70 of the powered medicament have been emptied. The inhaler is in consequence reusable. The cartridge may be removed or reinserted as required. - As shown in
Figure 6 , the underside of the periphery of thecartridge base 55 is provided with a plurality of equallyspaced cutouts 53, that are adapted to be engaged by thedrive cam 18 driven by thelever 30 to cause thecartridge base 55,base foil 60, perforatedlayer 80, liddingfoil 90 andupper cover 52 to be rotated through a small angle when thelever 30 is displaced in the anti-clockwise direction. Theupper cover 52 is also rotated by thedrive cam 18 through a small angle when thelever 30 is displaced in the clockwise direction. - It is however understood that more or less than ten
compartments 70 can be positioned on thebase foil 60 and thecartridge base 55 can include as many peripheral cutouts as are necessary to ensure that each compartment is indexed to the required position by displacement of thelever 30. Thebase foil 60 is positioned axially aligned on top of thecartridge base 55. - The
lower cover 51 has an arcuate slot 9 through which thedrive cam 18 extends to engage the cartridge base. Thelower cover 51 of thecartridge 50 has a central upstandingcircular spigot 84 that includes an internalupstanding ring 85. As shown inFigures 4 and5 a pair of radially alignedwedges spigot 84 and inner wall of thelower cover 51. When the base foil compartments 70 have been filled and covered by theperforated layer 80 and sealed by thelidding foil 90, the laminated cartridge assembly is lowered into thelower cover 51 with the wedge shapedopeners outer slots lidding foil layer 90 does not have slots on the inner and outer peripheries which means that the foil rests on thewedges cartridge 50 is completed by location of theupper cover 52 into locked engagement with thelower cover 51. As shown inFigure 7 , theupper cover 52 has a peripheral downwardly extendingskirt 49 with a rectangular cut-out 48 into which alug 108 on the end of thedrive cam 18 locates so movement of thedrive cam 18 causes a rotational movement of theupper cover 52. - As shown in
Figures 7 and10 , theupper cover 52 has a central taperedboss 95 that clips into thering 85 in thelower cover 51. A downwardly extendingannular flange 96 fits against the exterior of thering 85 allowing theupper cover 52 to oscillate relative to thelower cover 51. The upper surface of theupper cover 52 includes aviewing aperture 44 and anair inlet aperture 45. Afinger tab 46 extends down from the upper surface of the cover to provide ease of removal of thecartridge 50 from the inhaler body. The underside of theupper cover 52 also has an elongate downwardly extendingbar 47 that, in use, engages the top of thelidding foil 90 to push back the lidding foil onto theperforated layer 80,base foil 60 andbase 55 after the contents of a compartment have been ejected. Thebar 47 thus partially reseals the compartment. -
Figure 3 shows how thecartridge 50 can be lowered into the inhaler body 11. Thecartridge 50 is gripped by thefinger tab 46 and lowered into therecess 14 of the inhaler body 11 withoutlet slot 29 aligned with themouthpiece 26. The shape of thecartridge 50 is such that it can only be positioned in the inhaler in the correct position. Thelever 30, through the drive cam (not shown), engages thecutouts 53 in the underside of thecartridge base 55 so that movement of thelever 30 has the effect of causing rotational movement of thedisc base 55. The lever that drives thecartridge base 55 to rotate relative to thelower cover 51 of thecartridge 50 also has the effect of causing theupper cover 52 to oscillate on thelower cover 51 by contact between thelug 108 on thedrive cam 18 and the cut-out 48 in theupper cover 52. The connection between thelever 30 and drivecam 18 introduces a small degree of free play or neutral movement. - The role of the wedge shaped
openers Figures 10 and11 . As mentioned above, when the cartridge is assembled, the disc assembly sits in thelower cover 51 with the wedge shapedopeners lidding foil layer 90. As the lever is actuated to cause the disc assembly to rotate relative to thelower cover 51, the inclined ramp on the upper surface of theopeners lidding foil 90 at the inner and outer sections from the top of theperforated layer 80 thereby exposing the powder within thecompartment 70. The openers can either be positioned in a leading, central or trailing position in relation to themedicament compartment 70 on the assembly and as the disc continues to rotate, the openers lift the inner and outer sections of the lidding foil to expose the contents for removal upon inhalation and then allow the lidding foil to fall back into position against theperforated layer 80 thereby re-closing thecompartment 70. The trailingbar 47 on the underside of theupper cover 52 then pushes the foil back against the base foil to partially reseal the compartment. - The
lid 15 of the inhaler is shown in greater detail inFigures 2 ,12 and13 . The lid has a circular shapedclear cover 100 with aviewing tab 101 on one side and anarcuate window 102 on the opposite side. The circular shapedclear cover 100 is obscured except for anarea 103. There is a gap extending about 90° around theclear cover 100 defining theair inlet 19. The underside of the lid has acentral spigot 104 which supports aflow indicator 110 and aflap valve 112. As air is drawn into the inhaler through theair inlet 19, theflexible flap valve 112 pivots open as shown in detail B. Any attempt to blow air back through the inhaler is prevented by theflap valve 112 moving to the closed position shown in detail A. - As shown in
Figure 13 , theflow indicator 110 is in the form of anarcuate flag 113 that hasdownward projections 114, that reside ingrooves 116 in the underside of the lid. As air is drawn into theinhaler 10 it causes theflag 113 to move in thegrooves 116 and to rise up a ramp to assume a visible position through thearea 103 of thewindow 100. The ramp tends to hold theflag 113 in the operative position after inhalation. When thelever 30 is indexed to the closed position, the oscillating movement of the top of thecartridge 50 causes arcuate cut-outs projections 114 to return theflag 113 to the inoperative and less visible position. The incoming air current is sufficient to drive theflag 113 to the operative position. Thus, as shown inFigure 13 the airflow is such that when the user inhales on themouthpiece 26 air is drawn into theinhaler 10 via theair inlet 19 around the underside of thewindow 100 into the inhaler to move theflag 113 to the position shown inFigure 13b . At this stage with theflag 113 in the operative position the air flows in to the inhaler displacing the oneway valve 112 and into thecartridge 50. The air flows through theair inlet 45 at the top of the cartridge and out under the lidding foil that has been prized upwardly by theopeners perforated layer 80 across the top of thecompartment 70 and out through the radially outer section of the compartment through theperforated layer 80 and theinhalation aperture 27 andmouth piece 26. The air current is such that it causes turbulence causing the powder to be drawn through theperforated layer 80 to be entrained in the air for expulsion. Theperforated layer 80 has the role of preventing escape of powder without the air current so thus, if for some reason, thelidding foil 90 is removed from the compartment by accident theperforated layer 80 prevents escape of the powder and only allows powder escape when it is entrained in an air current. The perforations in thelayer 80 also assist to control the particle size of the released medicament. - The lid also includes the
small viewing tab 101 that exposes through magnification an arcuate line of numbering that would be positioned on thelidding foil 90 and exposed through thehole 44 in theupper cover 52. The numbering reflects the number ofrecesses 70 with unused doses so that the user of the inhaler can know how many doses remain in the cartridge. - The
inhaler 10 also includes a number of other features that reduce inadvertent additional dosage and reduce the likelihood of accidental displacement of the medicament. It is only on a full displacement of thelever 30 to the right as shown inFigure 3 that opens the next dose and indexes the cartridge so the dose is positioned in line with the airflow passageway. The lever is connected to an arcuate band thedrive cam 18 that locates on the inner surface of the body 11. The connection between thedrive lever 30 and drivecam 18 introduces a small degree of free play or neutral movement. The lever is coupled to the drive cam having an aperture 109 so that only full displacement of the lever to the right as shown inFigure 4 moves the aperture 109 in thedrive cam 18 into correct alignment with theaperture 27 of themouthpiece 26 to open the air passageway. When the lever returns to the left or closed position the drive cam moves to close off themouthpiece 26. - The
lever 30 that closes off the airflow passageway and does not open this passageway until the lever has again been displaced fully to the right. As thelever 30 is displaced theopeners lidding foil 90 from theperforated layer 80 to expose the radially inner and outer sections of recessedcompartment 70. By the time thelever 30 has moved to the fully displaced position thefoil 90 has been lifted from the radially inner and outer sections of thecompartment 70 to open the air passageway. At that time the air passageway is open to themouthpiece 26 allowing inhalation. If the lever is closed i.e. returned to its original position to the left without taking the dose that dose will then be lost because it will be indexed into an inoperative position when the lever has moved again. Thus reducing the possibility of unintentional additional dosing. - The
cover 52 that is positioned over thefoils openers lidding foil 90 off theperforated layer 80 an unadministered dose becomes effectively sealed in itscompartment 70 as it is indexed past the openers which allows the lidding foil to return to its former position with thebar 47 closing off thecompartment 70. - The
flap 112 operates as a one-way valve to ensure that exhalation does not have any effect on the medicament. The valve virtually prevents or at least minimises the amount of air that can be blown into the device so that exhalation does not dislodge or disturb a readied dose or for that matter disturb a dose that has not been administered. When in its uppermost position the oneway valve 112 closes the air flow pathway exit to minimise the possibility of air flow over the unadministered dose. - The shape of the cutouts in the periphery of the base is such that when the last dose has been dispensed the lever cannot further rotate the disc so that the user becomes aware that the cartridge is empty and can thus replace the cartridge.
-
Figures 15 to 17 illustrate a second embodiment that utilises a different cartridge which is shown inFigure 15 . Thecartridge 150 has a slittop foil layer 190 provided withradial slits 192 that define segments that correspond to the position of each compartment. Thetop foil layer 190 has acentral aperture 191 and is bonded to thelower foil 160 to seal off thecompartments 170. Acircular assembly 180 of fliptop members 181 is bonded to thetop foil 190. Theassembly 180 comprises a plastics moulding in the form of a plurality of radially extending fliptop members 181 that are interconnected by circumferentially extendingwebs 182. Each fliptop member 181 comprises a radiallyouter arm 184 that is joined to a V-shapedinner arm 185 by thewebs 182 that interconnect that fliptop member 181 to the adjacent flip top members. The underside of both the radially outer and inner arms include downwardly projecting triangular shapedlugs assembly 180 to thetop foil 190 means that each segment includes a segmentally shaped piece of foil with the skeletal framework of the fliptop members 181 transcribing the inner and outercircumferential edges assembly 180 is bonded to thetop foil 190, rotation of thedisc base 151 causes rotation of theassembly 180,top foil 190 andlower foil 160 in unison relative to thecover 195. - The assembly of the
disc base 151, twofoil layers top assembly 180 is then covered by aplastics cover 195 that has acentral aperture 196 and a downwardly extendingannular skirt 197 that covers the components. Anarcuate cutout 198 is provided in the periphery of theskirt 197 of thecover 195 through which a lever (not shown), similar to the first embodiment, can extend to engage thedisc base 151. The rotation of thedisc base 151 and foillayers top assembly 180 relative to thecover 195 is illustrated inFigure 16 . Anarcuate cutout 199 is provided in the periphery of theskirt 197 of thecover 195 which, prevents the base rotating in the wrong direction by engaging thedisc base 151. - Displacement of the lever rotates the
disc base 151 causing the inner andouter lugs top member 181 to ride up on radial projections on the base of the inhaler (not shown) to cause thearms top members 181 to flex upwardly as shown inFigure 17 about the central line orwebs 182. Upward flexing of the fliptop members 181 lifts thetop foil 190 from the radially inner and outer edges of thecompartments 170 causing an air passageway to form between the centre of thecartridge 150, the lifted inner fliptop arm 184 thecompartment 170 and the lifted outer fliptop arm 185. In this way the airflow passageway is defined by thetop foil 190, the fliptop member 181 and thecompartment 170. Thecover 195 of the cartridge has inclined up standingportions top member 181 in the elevated position as shown inFigure 17 . As thedisc base 151 is further rotated the undersurface of thecover 195 forces the previously opened fliptop members 181 down to the horizontal position, shown around the remainder of the periphery of the fliptop assembly 180 inFigure 15 . The radial slits 192 in thetop foil 190 facilitate the upward movement of the fliptop members 181 relative to the remainder of thefoil 190. - The flip
top assembly 180 has a dual role of displacing thetop foil 190 layer from thelower foil 160 and thus exposing eachcompartment 170 whilst at the same time forming a framework for an air passageway that flows from the aperture in the top of the lid of the inhaler down through the centre of the inhaler and along theradial arms outer arm 185 and through the mouthpiece in the periphery of the body. The fliptop members 181 lift thetop foil 190 off thelower foil 160 and the radial edges of the compartment and the skeletal structure of themembers 181 coupled with the foil surfaces provides the air passageway so that the user inhales through the mouthpiece drawing air down and into the inhaler and through the passageway. The air current picks up the powder in the exposedrecess 170. The powder is then entrained in the air to leave the inhaler via the mouthpiece. - In the third embodiment shown in
Figures 18 and19 , thedisc base 251 andlower foil 260 are provided with radially inner andouter cutouts last compartment outs disc opener 220 in the form of a bracket having aflat base 221 terminating anupstanding posts flanges 226. The posts andflanges 226 are positioned on the radially outer and radially inner end of theopener 220 and allow the opener to clip against the underside of thedisc base 251 with theflat base 221 in parallel sliding contact with the underside ofdisc base 251 and theflanges 226 extending across thelower foil 260 surface but beneath theupper foil 290. Thedisc opener 220 is located in thecover 250 of the cartridge in a manner that it cannot rotate with thedisc base 251 so that as the disc base is rotated the leading edges of theflanges 226 have the effect of lifting up the radially inner and outer edges of thetop foil 290 on theadjacent compartment 270. As the disc base is indexed to the operative position as shown inFigure 19 the radially inner and radially outer edges of thetop foil 290 are lifted clear of thecompartment 270 and the air passageway is defined by the compartment base and thetop foil 290 that has been raised at least adjacent the radially outer and radially inner edges of the compartment by thedisc opening flanges 226. - To ensure that the
top foil 290 lifts off asingle compartment 270 the radially outer 271 and radiallyinner edges 272 of eachcompartment 270 are at a position lower than the centre of thecompartment 273 so that thedisc opener flanges 226 only have to lift the radially inner 291 and radial outer 292 edges of the top foil level with thecentre 293. It is for this reason that thetop foil 290 is illustrated with what appear to be concentric rings. Thecentral ring 293 allows the radially inner and radially outer sections of thetop foil 290 to lift into the open position. This arrangement provides a narrow passageway whereby the central portion of thetop foil 290 remains above the recessedcompartment 270 and the air current to ensure that the air current is in close proximity to the powdered medicament. - When the
top foil 290 is bonded to thelower foil 260 there is no bond in the gap 268 between the first 264 and last 265 compartments (except for the compartment periphery - a sealing band surrounding the compartment) which means that it becomes a simple exercise to insert thedisc opening flanges 226 between the foil surfaces in that gap 268 to complete assembly. - The
cover 295 of thedisc 250 is provided with a raisedinclined section 296 over the position of thedisc opener 220 to accommodate the upstanding posts andflanges 226. - The inhaler is reusable, whilst the empty cartridges are discarded.
- Cartridges can be supplied with a range of dose number, medicament type and volume.
- Full and partially full cartridges can be loaded into and removed from the inhaler as required - either well before a dose is required or just prior to use.
- Loading of the cartridge does not open a dose for inhalation.
- The dose is opened and prepared for inhalation by simply sliding the indexing lever.
- The access to the mouthpiece is opened or closed by simply sliding the indexing lever.
- The possibility of unintentional additional dosing is minimised.
- Exhalation into the inhaler does not affect the effectiveness of the next dose from the cartridge.
- The inhaler via the cartridge has a "doses remaining" indicator.
- The inhaler has an indicator to indicate correct dosage received.
- The cartridge covers and foils protect the user from residues in opened compartments of the cartridge.
- Although in the preferred embodiments the inhaler comprises an inhaler body and disposable cartridge it is understood that in a simple form the inhaler may simply be like the cartridge that is without the external body. The cartridge would include a mechanism to displace the compartments and cause opening of each compartment when it is aligned with an outlet aperture that would serve as the mouthpiece.
- The inhaler may be used to provide medications selected from the following therapy areas: antiinfluenza, analgesic, anti-anginal preparation, antiallergic, anti-infective, anticancer, antihistamine, anti-inflammatory, antitussive, bronchodilator, cortiscosteroid, diuretic, anticholinergic, hormone, xanthine, osteoporosis, hypertension, therapeutic protein or peptide, vaccine, diagnostic agent or gene therapy agent.
- The inhaler may be used to provide medications selected from the following group: zanamivir, codeine, dihydromorphine, ergotamine, fentanyl, morphine, diltiazem, cromoglycate, ketotifen, nedocromil, cephalosporins, penicillins, streptomycin, sulphonamides, tetracyclines, pentamidine, methapyrilene, beclomethasone dipropionate, fluticasone propionate, flunisolide, budesonide, rofleponide, mometsasone furoate, triamcinolone acetonide, noscapine, albuterol sulphate, salmeterol xinafoate, salmeterol, ephedrine, adrenaline, fenoterol, formoterol, isoprenaline, metaproterenol, phenylephrine, phenylpropanolamine, pirbuterol acetate, reproterol hydro chloride, rimiterol, terbutaline sulphate, isoetharine, tulobuterol, orciprenaline, adenosine 2a agonists, α4 integrin inhibitors, amiloride, ipratropium, tiotropium, atropine or oxitropium, cortisone, hydrocortisone or prednisolone, aminophylline, choline theophyllinate, lysine theophyllinate or theophylline, insulin or glucagon, or salts, esters, or solvates thereof, alone or in combination.
Claims (21)
- An inhaler (10) for delivering metered doses of powdered medicament, the inhaler (10) having a plurality of compartments (70) spaced in an annular array and each containing a metered dose of the medicament, a lever (30) to displace the compartments (70) one by one into line with an inhalation aperture (27) that constitutes a mouthpiece (26), each compartment (70) including radially inner and outer edges, the plurality of compartments (70) being closed by a) sealing layer (90), characterised in that the inhaler (10) has a mechanism (86, 87) adapted to lift the inner and outer edges of the sealing layer (90) off the radially inner and outer edges of each compartment (70) one by one as it is indexed to align with the inhalation aperture (27) to open an air passageway defined by the compartment (70) and the sealing layer (90) so that, in use, on inhalation through the mouthpiece (26), air flow in the air flow passageway picks up and entrains the powder in the compartment (70) to be drawn with the air out of the inhaler (10) though the mouthpiece (26).
- The inhaler (10) according to claim 1 wherein each compartment (70) is covered by a perforated layer (80) and the sealing layer (90) covers the perforated layer (80) with the lifting mechanism (86, 87) adapted to lift the inner and outer edges of the sealing layer (90) from the perforated layer (80).
- The inhaler (10) according to claim 1 or claim 2 wherein the lever (30) is moveable from an inoperative position to an operative position in which one compartment (70) is indexed to align with the inhalation aperture (27) and the inner and outer edges of the sealing layer (90) are lifted off the compartment (70), the lever (30) being returnable to the in operative position.
- The inhaler (10) according to claim 3 wherein the inhaler (10) has a sealing bar (47) that pushes down the inner and outer edges of the sealing layer (90) as the lever (30) is returned to the inoperative position.
- The inhaler (10) according to any one of claims 1 to 4 wherein the inhaler (10) comprises a body (11) adapted to receive a cartridge (50) that carries the compartments (70), the inhalation aperture (27) being provided in the body (11) in a position aligned with an outlet aperture (29) in the cartridge (50), and the lever (30) being mounted on the body (11) to be displaceable from the inoperative position to the operative position in which a fresh compartment (70) is displaced and opened so that the opened compartment (70) is aligned with the inhalation aperture (27).
- The inhaler according to claim 5 wherein the lever (30) includes a component that closes the inhalation aperture (27) in the inoperative position and opens the aperture (27) in the operative position.
- The inhaler (10) according to claims 5 or 6 wherein the body (11) defines a recess (14) into which the cartridge (50) is located, a lid (15) being pivoted to the body (11) to close off the recess (14).
- The inhaler (10) according to claim 7 wherein the lid (15) includes an air entry aperture (19).
- The inhaler (10) according to claim 8 wherein the lid (15) includes indicator means (110) to provide a visual indication that air has been drawn through the inhaler (10).
- The inhaler (10) according to claim 9 wherein the indicator means (110) comprises a member (113) displaceable in response to a minimum air flow.
- The inhaler (10) according to claim 10 wherein the member (13) is displaceable from a start position to a finish position, the finish position reflecting minimum air flow.
- The inhaler (10) according to any one of claims 5 to 11 wherein the cartridge (50) comprises a disc assembly mounted within upper and lower covers (52, 51), the disc assembly being axially rotatable relative to the lower cover (51).
- The inhaler (10) according to claim 12 wherein the disc assembly comprises the array of spaced compartments (70) sealed by the sealing layer (90), which is disc shaped.
- The inhaler (10) according to claim 13 wherein the array of compartments (70) are formed in a metal foil disc shaped sheet (60) that is positioned on a similarly formed disc shaped base member (55).
- The inhaler (10) according to any one of claims 12 to 14 wherein the lifting mechanism comprises a pair of spaced projections (86, 87), and wherein the lower cover (51) has said pair of spaced projections (86, 87) that extend past slots (57, 58, 62, 63, 82, 83) in the disc assembly to engage the underside of the sealing layer (90) whereby rotation of the disc assembly past the projections (86, 87) causes the projections (86, 87) to lift the sealing layer (90) off the inner and outer edges of the compartments (70) one by one as the compartments (70) move over the projections (86, 87).
- The inhaler (10) according to claims 12 to 15 when dependant on claim 11 wherein the upper cover (52) is capable of oscillating relative to the lower cover (51), the oscillation causing rotation of the member (113) to the start position.
- The inhaler (10) according to any one of claims 1 to 11 wherein the lifting mechanism comprises a flip top member (181) secured to the sealing layer (190) and having portions (184, 185) adapted to flex upwardly relative to the compartment (170) to lift the sealing layers (190) off the inner and outer edges of the compartment (170).
- The inhaler (10) according to claim 17 wherein the inhaler (10) includes means to flex the portions (184, 185) upwardly as the compartment (170) is displaced relative to the inhaler (10).
- The inhaler (10) according to any one of claims 1 to 11 wherein the lifting mechanism comprises an opener in the form of wedge shaped members (86, 87) mounted spaced apart on a plate which is positioned beneath the array of compartments (70), the wedge shaped members (86, 87) engaging the underside of the sealing layer (90), the plate being fixed relative to the inhaler (10) so that displacement of the array of compartments (70) to relative to the inhaler (10) causes each compartment (70) to move past the wedge shaped members (86, 87) to lift the sealing layer (90) off the inner and outer edges of the compartment (70).
- The inhaler (10) according to any one of the preceding claims wherein the inhaler (10) has a one way valve (112) that allows air to be drawn in through the inhaler (10) and out of the mouthpiece (26) but prevents flow of air in the reverse direction.
- The inhaler (10) according to any one of the preceding claims wherein ten compartments (70) are spaced in an array.
Applications Claiming Priority (9)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AUPR7767A AUPR776701A0 (en) | 2001-09-19 | 2001-09-19 | An inhaler |
AUPR7766A AUPR776601A0 (en) | 2001-09-19 | 2001-09-19 | An inhaler |
AUPR776601 | 2001-09-19 | ||
AUPR776701 | 2001-09-19 | ||
AUPR7830A AUPR783001A0 (en) | 2001-09-19 | 2001-09-19 | An inhaler |
AUPR783001 | 2001-09-19 | ||
AUPR293802 | 2002-06-13 | ||
AUPR293802 | 2002-06-13 | ||
PCT/AU2002/001284 WO2003024514A1 (en) | 2001-09-19 | 2002-09-18 | An inhaler |
Publications (3)
Publication Number | Publication Date |
---|---|
EP1427465A1 EP1427465A1 (en) | 2004-06-16 |
EP1427465A4 EP1427465A4 (en) | 2012-01-25 |
EP1427465B1 true EP1427465B1 (en) | 2016-01-13 |
Family
ID=32329889
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP02764384.0A Expired - Lifetime EP1427465B1 (en) | 2001-09-19 | 2002-09-18 | Powder inhaler |
Country Status (3)
Country | Link |
---|---|
EP (1) | EP1427465B1 (en) |
DK (1) | DK1427465T3 (en) |
ES (1) | ES2567194T3 (en) |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB9012870D0 (en) * | 1990-06-08 | 1990-08-01 | Glaxo Group Ltd | Device |
GB2264237A (en) * | 1992-02-05 | 1993-08-25 | Robert Edward Newell | An inhaler |
AUPR020400A0 (en) * | 2000-09-19 | 2000-10-12 | Glaxo Wellcome Australia Ltd | Inhalation device |
-
2002
- 2002-09-18 EP EP02764384.0A patent/EP1427465B1/en not_active Expired - Lifetime
- 2002-09-18 ES ES02764384.0T patent/ES2567194T3/en not_active Expired - Lifetime
- 2002-09-18 DK DK02764384.0T patent/DK1427465T3/en active
Also Published As
Publication number | Publication date |
---|---|
DK1427465T3 (en) | 2016-04-11 |
EP1427465A1 (en) | 2004-06-16 |
ES2567194T3 (en) | 2016-04-20 |
EP1427465A4 (en) | 2012-01-25 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CA2460904C (en) | An inhaler for delivering metered doses of powdered medicament | |
US6679254B1 (en) | Inhalation device | |
US6029663A (en) | Dry powder inhaler delivery system | |
EP0883414B1 (en) | Inhalation device | |
EP1294420B2 (en) | Pre-metered dose magazine for breath-actuated dry powder inhaler | |
US6915802B1 (en) | Medicament pack | |
US20190275269A1 (en) | Dry Powder Inhaler | |
EP2328645B1 (en) | Dry powder inhalers with rotating piercing mechanisms and related devices and methods | |
US20130118490A1 (en) | Inhalers with airway disks having discrete airway channels and related disks and methods | |
US8887722B2 (en) | Inhaler mechanisms with radially biased piercers and related methods | |
US7089935B1 (en) | Inhalation device | |
EP1318849B1 (en) | Inhalation device | |
WO2005030305A1 (en) | Assembly for opening medicament containers, particularly containers for a powdered medicament | |
EP1427465B1 (en) | Powder inhaler | |
WO2002000279A1 (en) | Delivery device | |
AU2002301078B1 (en) | An Inhaler |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
17P | Request for examination filed |
Effective date: 20040408 |
|
AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR IE IT LI LU MC NL PT SE SK TR |
|
AX | Request for extension of the european patent |
Extension state: AL LT LV MK RO SI |
|
REG | Reference to a national code |
Ref country code: HK Ref legal event code: DE Ref document number: 1068007 Country of ref document: HK |
|
A4 | Supplementary search report drawn up and despatched |
Effective date: 20111227 |
|
RIC1 | Information provided on ipc code assigned before grant |
Ipc: A61M 15/00 20060101AFI20111220BHEP |
|
GRAP | Despatch of communication of intention to grant a patent |
Free format text: ORIGINAL CODE: EPIDOSNIGR1 |
|
INTG | Intention to grant announced |
Effective date: 20150709 |
|
RIN1 | Information on inventor provided before grant (corrected) |
Inventor name: ALLAN, ROBERT, DAVID Inventor name: PIKE, GREGORY, CHARLES |
|
GRAS | Grant fee paid |
Free format text: ORIGINAL CODE: EPIDOSNIGR3 |
|
GRAA | (expected) grant |
Free format text: ORIGINAL CODE: 0009210 |
|
RAP1 | Party data changed (applicant data changed or rights of an application transferred) |
Owner name: ADVENT PHARMACEUTICALS PTY LIMITED |
|
AK | Designated contracting states |
Kind code of ref document: B1 Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR IE IT LI LU MC NL PT SE SK TR |
|
REG | Reference to a national code |
Ref country code: GB Ref legal event code: FG4D |
|
REG | Reference to a national code |
Ref country code: CH Ref legal event code: EP |
|
REG | Reference to a national code |
Ref country code: IE Ref legal event code: FG4D |
|
REG | Reference to a national code |
Ref country code: AT Ref legal event code: REF Ref document number: 770083 Country of ref document: AT Kind code of ref document: T Effective date: 20160215 |
|
REG | Reference to a national code |
Ref country code: DE Ref legal event code: R096 Ref document number: 60247741 Country of ref document: DE |
|
REG | Reference to a national code |
Ref country code: DK Ref legal event code: T3 Effective date: 20160407 |
|
REG | Reference to a national code |
Ref country code: PT Ref legal event code: SC4A Free format text: AVAILABILITY OF NATIONAL TRANSLATION Effective date: 20160407 |
|
REG | Reference to a national code |
Ref country code: CH Ref legal event code: NV Representative=s name: FIAMMENGHI-FIAMMENGHI, CH |
|
REG | Reference to a national code |
Ref country code: ES Ref legal event code: FG2A Ref document number: 2567194 Country of ref document: ES Kind code of ref document: T3 Effective date: 20160420 Ref country code: NL Ref legal event code: FP |
|
REG | Reference to a national code |
Ref country code: SE Ref legal event code: TRGR |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: FI Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20160113 Ref country code: GR Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20160414 |
|
REG | Reference to a national code |
Ref country code: DE Ref legal event code: R097 Ref document number: 60247741 Country of ref document: DE |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: EE Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20160113 |
|
PLBE | No opposition filed within time limit |
Free format text: ORIGINAL CODE: 0009261 |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: SK Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20160113 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: CZ Payment date: 20160916 Year of fee payment: 15 |
|
26N | No opposition filed |
Effective date: 20161014 |
|
REG | Reference to a national code |
Ref country code: HK Ref legal event code: GR Ref document number: 1068007 Country of ref document: HK |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: BG Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20160413 Ref country code: BE Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20160930 |
|
REG | Reference to a national code |
Ref country code: DE Ref legal event code: R119 Ref document number: 60247741 Country of ref document: DE |
|
REG | Reference to a national code |
Ref country code: DK Ref legal event code: EBP Effective date: 20160930 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: SE Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20160919 Ref country code: MC Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20160113 |
|
REG | Reference to a national code |
Ref country code: CH Ref legal event code: PL |
|
REG | Reference to a national code |
Ref country code: SE Ref legal event code: EUG |
|
REG | Reference to a national code |
Ref country code: NL Ref legal event code: MM Effective date: 20161001 |
|
GBPC | Gb: european patent ceased through non-payment of renewal fee |
Effective date: 20160918 |
|
REG | Reference to a national code |
Ref country code: IE Ref legal event code: MM4A |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: NL Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20161001 |
|
REG | Reference to a national code |
Ref country code: FR Ref legal event code: ST Effective date: 20170531 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: GB Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20160918 Ref country code: LI Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20160930 Ref country code: CH Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20160930 Ref country code: IE Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20160918 Ref country code: FR Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20160930 Ref country code: DE Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20170401 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: LU Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20160918 Ref country code: IT Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20160918 Ref country code: PT Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20170619 |
|
REG | Reference to a national code |
Ref country code: AT Ref legal event code: MM01 Ref document number: 770083 Country of ref document: AT Kind code of ref document: T Effective date: 20160918 |
|
REG | Reference to a national code |
Ref country code: BE Ref legal event code: FP Effective date: 20160407 Ref country code: BE Ref legal event code: MM Effective date: 20160930 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: DK Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20160930 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: AT Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20160918 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: CZ Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20170918 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: ES Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20170919 Ref country code: CY Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20160113 |
|
REG | Reference to a national code |
Ref country code: ES Ref legal event code: FD2A Effective date: 20180625 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: TR Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20160113 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: ES Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20160919 |
|
REG | Reference to a national code |
Ref country code: AT Ref legal event code: UEP Ref document number: 770083 Country of ref document: AT Kind code of ref document: T Effective date: 20160113 |